Membrane TNF confers protection to acute mycobacterial infection.
Membrane TNF confers protection to acute mycobacterial infection.
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DOI：
10.1186/1465-9921-6-136
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发表时间：
2005-11-14
影响因子：
5.8
通讯作者：
Ryffel B
中科院分区：
文献类型：
--
作者：
Fremond C;Allie N;Dambuza I;Grivennikov SI;Yeremeev V;Quesniaux VF;Jacobs M;Ryffel B
肿瘤坏死因子对控制分枝杆菌感染至关重要，因为肿瘤坏死因子缺陷(KO)会因坏死性肺炎感染失控而迅速死亡。在这里，我们研究了膜上的肿瘤坏死因子在具有不可切割和调节的等位基因(mem-TNF)的敲入小鼠的宿主抵抗中的作用。用结核分枝杆菌H37Rv(100CFU)滴鼻感染C57BL/6、肿瘤坏死因子KO和mem-肿瘤坏死因子小鼠，观察小鼠的存活、细菌载量、肺组织病理学和免疫学指标。用骨髓和淋巴细胞移植检测膜上肿瘤坏死因子对肿瘤坏死因子KO小鼠的抵抗作用。当肿瘤坏死因子-KO小鼠在4-5周内死于感染时，mem-TNF小鼠正常招募T细胞和巨噬细胞，在肺部形成成熟的肉芽肿，并控制了急性结核分枝杆菌感染。然而，在感染的慢性期，mem-TNF小鼠在大约150天后死于播散性感染并伴有坏死性肺炎。用mem-肿瘤坏死因子来源的骨髓细胞而不是淋巴细胞重建受照射的肿瘤坏死因子-KO小鼠，使宿主对结核分枝杆菌感染具有抵抗力。膜表达的肿瘤坏死因子足以使细胞-细胞信号和控制急性结核分枝杆菌感染。来自mem-tf小鼠的骨髓细胞，而不是来自mem-tm-tf小鼠的淋巴细胞，对tm-ko小鼠的感染具有抵抗力。慢性炎症可能干扰肿瘤坏死因子介导的细胞-细胞信号的长期感染控制，另外还需要可溶性肿瘤坏死因子。
Tumour necrosis factor (TNF) is crucial for the control of mycobacterial infection as TNF deficient (KO) die rapidly of uncontrolled infection with necrotic pneumonia. Here we investigated the role of membrane TNF for host resistance in knock-in mice with a non-cleavable and regulated allele (mem-TNF). C57BL/6, TNF KO and mem-TNF mice were infected with M. tuberculosis H37Rv (Mtb at 100 CFU by intranasal administration) and the survival, bacterial load, lung pathology and immunological parameters were investigated. Bone marrow and lymphocytes transfers were used to test the role of membrane TNF to confer resistance to TNF KO mice. While TNF-KO mice succumbed to infection within 4–5 weeks, mem-TNF mice recruited normally T cells and macrophages, developed mature granuloma in the lung and controlled acute Mtb infection. However, during the chronic phase of infection mem-TNF mice succumbed to disseminated infection with necrotic pneumonia at about 150 days. Reconstitution of irradiated TNF-KO mice with mem-TNF derived bone marrow cells, but not with lymphocytes, conferred host resistance to Mtb infection in TNF-KO mice. Membrane expressed TNF is sufficient to allow cell-cell signalling and control of acute Mtb infection. Bone marrow cells, but not lymphocytes from mem-TNF mice confer resistance to infection in TNF-KO mice. Long-term infection control with chronic inflammation likely disrupting TNF mediated cell-cell signalling, additionally requires soluble TNF.
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影响因子：
5.4
作者：
Kusters, S;Tiegs, G;Grell, M
通讯作者：
Grell, M
影响因子：
5
作者：
Jacobs, M;Marino, MW;Ryffel, B
通讯作者：
Ryffel, B
DOI：
10.1084/jem.175.4.1111
发表时间：
1992-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chan J;Xing Y;Magliozzo RS;Bloom BR
通讯作者：
Bloom BR
影响因子：
4.4
作者：
Botha, T;Ryffel, B
通讯作者：
Ryffel, B
影响因子：
2.9
作者：
GREEN, LC;WAGNER, DA;TANNENBAUM, SR
通讯作者：
TANNENBAUM, SR